The present invention relates to the delivery of a medicament to the intestine. More particularly, the present invention relates to a system and method for delivering a medicament to the intestine by ingestion which is capable of delivering that medicament to the patient or animal for an extended period of time.
There have been a number of attempts to provide a system for delivering a medicament to the intestine which involve the oral ingestion of the medicament. The many benefits of such a system are summarized, for instance, in U.S. Pat. Nos. 3,901,232, 4,627,851, and 4,642,230, all of which are hereby incorporated herein in their entirety by this specific reference thereto. These same references characterize many of the disadvantages of prior attempts to provide such systems, and the following brief summary of the pharmacokinetics of certain such systems and their disadvantages will suffice to provide an illustration of the motivation for the present invention.
Although the primary function of the small intestine is absorption, making that organ an ideal candidate for administration of a medicament or therapeutic agent, a number of factors combine to limit the use of that mode of delivery. For instance, the pH of the duodenal portion of the small intestine is about 4 to 5, but pH becomes more alkaline progressively farther along the length of the intestine, and the effect of pH on the bioavailability of many medicaments is well documented. The flora of the entire gastrointestinal tract may inactivate certain medicaments or otherwise reduce their absorption or bioavailability, and the digestive enzymes produced in the intestinal mucosa have the same effect on certain medicaments. Further, although passage through the small intestine is slow compared, for instance, to passage through the oral cavity or stomach, an orally ingested medicament does pass through, and eventually out of, the intestine, making administration of the medicament over a sustained period of time problematical.
It is these problems, particularly the latter, with which the present invention is concerned. Several prior art patents describe delivery systems which purport to address the problem of passage through the gastrointestinal tract and administration of a medicament over extended periods, but those references appear to do so in less then satisfactory fashion. For instance, U.S. Pat. Nos. 3,844,285 and 4,623,345 describe devices enclosing a medicament which, after ingestion, open to release the medicament in the gastrointestinal tract, the open container acting to retain the device in the gastrointestinal tract by physical engagement of the mucosa. Such devices remain in the gastrointestinal tract even after all the medicament has been released because of that engagement. As described in the above-incorporated U.S. Pat. No. 4,642,230, it is also known to use weights in a device in which the medicament is contained to retain the device within the gastrointestinal tract. However, the weight is generally a heavy metal and, even if coated to prevent oxidation of the metal, sooner or later, the ingestion of heavy metals will have deleterious effects. Neither such consequence is generally considered acceptable in the case of human patients.
Another problem relating to passage of the medicament through the intestine is that it is often necessary to coat the medicament for passage through the stomach. Such "enteric" coatings are of particular use in the case of those medicaments which are destroyed or inactivated by the acidic contents of the stomach or which cause gastric irritation. However, many enteric-coated medicaments resist dissolution in the intestine as well as the stomach such that comparatively little of the medicament may be absorbed before the coated medicament is passed. Other problems with such medicaments are characterized in L. Z. Benet and L. B. Sheiner, "Pharmacokinetics: The Dynamics of Drug Absorption, Distribution, and Elimination," in A. G. Gilman, et al. (Eds.), Goodman & Gilman's The Pharmacological Basis of Therapeutics (7th Ed.), New York: MacMillan Publishing Co., pp. 3-34 (1985), hereby incorporated in its entirety by this specific reference thereto.
It is, therefore, an object of the present invention to provide an improved system and method for delivery of a medicament in the intestine which overcomes the above-described disadvantages and limitations of prior known systems.
It is a particular object of the present invention to provide a filament system and method for delivery of a medicament in the intestine over an extended period of time.
It is another object of the present invention to provide a filament system and method for delivery of a medicament in the intestine for both topical and systemic therapy.
It is another object of the present invention to provide a filament system and method for delivery of a medicament in the intestine which does not release the medicament in the gastrointestinal tract until the system reaches the intestine.
It is another object of the present invention to provide a filament system and method for delivery of a medicament to a specific location in the intestine as desired to effect topical therapy or to maximize absorption and/or bioavailability of the medicament for systemic therapy.
Yet another object of the present invention is to provide a filament system and method for retarding the passage of the reservoir from which the medicament is released through the intestine, thereby extending the period of time over which therapeutically effective doses of the medicament& are delivered.
It is another object of the present invention to provide a filament system and method by which the reservoir of medicament to be released at a specific location in the intestine is continually replenished by the passage of the filament through the intestine.
It is another object of the present invention to provide a filament system and method in which the reservoir from which the medicament is delivered does not remain in the gastrointestional tract permanently, but which is nevertheless capable of delivering effective dosage levels of the medicament for extended periods of time.
Other objects, and the advantages, of the present invention will be made clear to those skilled in the art by the following detailed description of a preferred embodiment thereof.